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Causal power of cortical neural ensembles: mechanisms and utility for brain perturbations

Award Number: R01MH127375
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Causal power of cortical neural ensembles: mechanisms and utility for brain perturbations - PROJECT SUMMARY Understanding the causal interactions in large neural ensembles is key for developing techniques to alter cognitive behavior through targeted manipulation of the brain. This is a challenging goal because commonly used methods for recording neural responses in the human brain do not provide information about physical connections of neurons and allow only extremely sparse sampling of neurons in a circuit (typically <1%). Here, we develop an innovative path forward using a multi-disciplinary approach that combines recent theoretical and experimental advances by the two PIs (Kiani and Mazzucato). In Aim 1, we introduce a novel theoretical framework to infer a map of causal functional connectivity (CFC) based on sparse sampling from neurons in a circuit. Our framework successfully recovers the structure of functional interactions, identifies hub neurons in the circuit, and has multi-scale properties that make it applicable on a variety of data, ranging from spiking of individual neurons to aggregated spiking of clusters of neighboring neurons to local field potentials. In Aim 2, we test if the CFC inferred from a population of simultaneously recorded prefrontal neurons successfully predicts how microstimulation perturbs neural activity in the circuit. Specifically, we show the existence of hub neural clusters, identified through CFC, whose microstimulation has large and predictable impacts on the population response dynamics. Finally, in Aim 3, we explore if the CFC and perturbation effects at rest predict how microstimulation alters behavior during a perceptual decision-making task. We hypothesize that resting CFC combined with the population activity prior to microstimulation successfully predicts the effect of microstimulation both on the circuit activity and the behavior. The approach, data and analyses proposed in each of these aims are novel and the combination will provide a practical solution for a long-standing problem in systems neuroscience.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $579,151 )
2026	2026	NEW YORK UNIVERSITY	70 WASHINGTON SQ S FL 11	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	5	4/13/2026	NON-COMPETING CONTINUATION	$579,151
														Subtotal = $579,151

Issue Date FY: 2025 ( Subtotal = $585,282 )
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	4	9/18/2025	NON-COMPETING CONTINUATION	$87,793
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	4	3/5/2025	NON-COMPETING CONTINUATION	$497,489
														Subtotal = $585,282

Issue Date FY: 2024 ( Subtotal = $592,527 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	3	8/14/2024	NON-COMPETING CONTINUATION	$59,253
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	3	1/31/2024	NON-COMPETING CONTINUATION	$533,274
														Subtotal = $592,527

Issue Date FY: 2023 ( Subtotal = $600,124 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	2	2/2/2023	NON-COMPETING CONTINUATION	$600,124
														Subtotal = $600,124

Issue Date FY: 2022 ( Subtotal = $621,001 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	000	1	3/11/2022	NEW	$560,409
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Mental Health Research Grants	001	1	6/27/2022	NEW	$60,592
														Subtotal = $621,001

Grand Total All Awards = $2,978,085

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Causal power of cortical neural ensembles: mechanisms and utility for brain perturbations

Award Number: R01MH127375

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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